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Biomedical subjects

M Kawamura

Publications and source records attributed to M Kawamura.

At least 289 records · Page 16Linked to original sources

Enhanced expression of platelet-derived growth factor-beta receptor by high glucose. Involvement of platelet-derived growth factor in diabetic angiopathy.

Coronary heart disease is a major complication of diabetic subjects, and platelet-derived growth factor (PDGF) has been implicated in the development of atherosclerosis. We investigated the effects of high glucose on expression of PDGF-beta receptor. In a binding assay with 125I-labeled PDGF-BB homodimer, high concentrations of glucose increased high-affinity binding of PDGF-BB on human monocyte-derived macrophages and rabbit aortic medial smooth muscle cells. Northern blot analysis confirmed the enhanced effect of glucose on expression of PDGF-beta receptor mRNA in human monocyte-derived macrophages. The protein kinase C inhibitor, staurosporin, completely suppressed an increase in PDGF-BB binding by high glucose, and high glucose significantly activated protein kinase C. These results indicated that PDGF-beta receptor expression was enhanced by high glucose through the activation of protein kinase C. Furthermore, we observed similar effects of high glucose on both PDGF-beta receptor expression and protein kinase C activation in rat mesangial cells and human capillary endothelial cells. Our results suggest that stimulation of the PDGF system is significantly involved in the development not only of diabetic atherosclerosis but also of microangiopathy.

Alkaloids↗

[Reconstruction of chest wall defects with autogenous ribs grafts].

Three methods of chest wall reconstruction using autogenous rib grafts were reported. Fresh non-vascularized autogenous rib graft, vascularized autogenous ribs with muscle-flap, and pasteurized autogenous rib grafts were the materials used in these techniques. They are less convenient than those with artificial materials but afterwards physiologically more natural chest wall will be reconstructed. The third method (pasteurized rib graft) was applied to 22-year-old female with large recurrent desmoid tumor. Six resected ribs were heated in the saline at 60 degrees C for 30 min. and three of them were returned to the former position. Though tumor cells and bacteria are killed under this condition, these heated bone can be revascularized and replaced by normal bone as early as fresh non-vascularized rib graft.

Adult↗

Antithrombotic effects of TAK-029, a novel GPIIb/IIIa antagonist, in guinea pigs: comparative studies with ticlopidine, clopidogrel, aspirin, prostaglandin E1 and argatroban.

The antithrombotic and bleeding time (BT)-prolonging effects of TAK-029, a novel glycoprotein IIb/IIIa antagonist, were characterized and compared with those of conventional antithrombotic agents in guinea pigs. TAK-029 potently inhibited the binding of fibrinogen and von Willebrand factor to purified human GPIIb/IIIa with IC50 values of 0.67 +/- 0.03 and 0.33 +/- 0.04 nM; it also inhibited human platelet aggregation induced by various aggregating agents with IC50 values of 29 to 38 nM. The in vitro antiplatelet effect of TAK-029 was potent in humans, guinea pigs and monkeys. When TAK-029 was given p.o. to guinea pigs, severe prolonging of BT (>1800 sec) was not observed with plasma concentrations of TAK-029 that inhibited ex vivo platelet aggregation by < 100%. The p.o. administration of TAK-029, ticlopidine and clopidogrel prolonged BT to the same extent, in parallel with their inhibition of ex vivo platelet aggregation. TAK-029 inhibited ex vivo platelet adhesion and thrombus formation in an arteriovenous shunt model more strongly than ticlopidine, clopidogrel and aspirin at doses causing similar prolongations of BT. In a balloon catheter-induced carotid thrombosis model, i.v. administration of TAK-029 significantly inhibited thrombus formation without prolonging BT. At doses that caused an incomplete antithrombotic effect, PGE1-alpha-cyclodextrin and argatroban produced hypotension and prolongation of BT, respectively. TAK-029 may be effective in patients suffering from arterial thrombotic diseases, which are refractory to these conventional antithrombotic agents.

Alprostadil↗

Homozygous deletions of p16/MTS1 and p15/MTS2 genes are frequent in t(1;19)-negative but not in t(1;19)-positive B precursor acute lymphoblastic leukemia in childhood.

We analyzed 60 B precursor acute lymphoblastic leukemia (ALL) primary samples and 15 cell lines for homozygous deletions of p16 and p15 genes and mutations of p16 gene. These included five cell lines and 13 primary samples with the t(1;19)(q23;pl3), and eight primary samples with the t(9;22)(q34;qll). Of 10 cell lines without t(1;19), homozygous deletion of both p16 and p15 genes was found in eight cell lines (80%), and a rearrangement of p16 in one cell line (10%). In contrast, only one (20%) of the five cell lines with t(1;19) showed homozygous deletion or rearrangement of p16/p15 gene. Thirteen of 60 (22%) primary samples demonstrated p16 gene homozygous deletion. No case with t(1;19) showed homozygous deletion of p16 gene (0/13, 0%), while cases without t(1;19) showed considerable incidence of p16 gene homozygous deletion (13/47, 28%). These results suggest that the incidence of deletions of p16 gene differs according to the subtypes of B precursor ALL. We also compared the frequency of p16 gene homozygous deletion between the patients at diagnosis and at relapse. Nine of 45 (20%) samples at diagnosis and four of 22 (18%) samples at relapse showed p16 homozygous deletions. The similarity of the rate in these two groups raises the question of the role of p16 gene in progression of B precursor ALL. Mutations were found in three of the primary cases (5%); the mutations included two nonsense mutations at codon 72 and one missense mutation at codon 98. All the mutations found in this study were heterozygous, and the clinical relevance of p16 gene mutation is yet to be determined in these case

Base Sequence↗

[Removal ability of IgG anti-GQ1b antibody in immunoadsorption therapy for Fisher syndrome--comparison of the removal ability between tryptophane column and phenylalanine column].

Anti-GQ1b antibody seems to be a pathogenetic factor in the development of Fisher syndrome (FS). Although several patients received immunoadsorption therapy (IAT), whether it can remove the autoantibody has not yet been clarified. We treated two patients with FS by IAT using tryptophane column (TR-C) and phenylalanine column (PH-C) (TR-C; 9 times altogether in 2 patients, PH-C: twice altogether in 2 patients), and compared the removal ability of IgG anti-GQ1b antibody and immunoglobulin between TR-C and PH-C. TR-C removed the IgG anti-GQ1b antibodies, IgG, IgA and IgM more than PH-C did. TR-C removed the IgG anti-GQ1b antibody more selectively than non-specific immunoglobulin. In practicing IAT on FS, the use of TR-C rather than PH-C is recommended in view of the removal ability of the autoantibody.

Adult↗

[Prognosis of hepatic metastasis from colorectal cancer following arterial infusion chemotherapy--assessment from the percentage of tumor involved area and tumor markers].

Prognosis of hepatic metastasis from colorectal cancer following arterial infusion chemotherapy was studied from the percentage of tumor involved area (PTIA) and tumor markers. The PTIA was calculated by the following formula: sigma S'/ sigma S, with S' as the tumor area and S as the liver area on each CT slice. The PTIA was 0.76 to 31.1%, and the average was 6.84%. As for the correlation between the PTIA and the prognosis, a statistically significant reverse correlation was found in the cases of death (r = -0.455, p < 0.05, n = 22). In the tumor regression effect of NC cases, the 50% survival time was 24.4 months in cases showing a decrease in CEA or CA19-9 and 18.7 months in the cases showing an increase. Prognosis of the former cases was significantly better than that of the latter cases (p < 0.05). Therefore, PTIA and the decrease in CEA or CA19-9 in the cases of hepatic arterial infusion chemotherapy for metastasis from colorectal cancer seemed important factors reflecting prognosis.

Antineoplastic Agents↗

[Simple partial seizure consisting of complex visual hallucinations due to left temporo-occipital lesion].

We report a case of simple partial seizure consisting of elementary visual hallucinations and complex visual hallucinations due to left temporo-occipital lesion. The patient was a 45-year-old right-handed female who has been suffering from paroxysmal visual hallucinations in her right visual field for 15 days before admission. The properties of the hallucinations included several round colorful figures, the upper torsos of people in red, and green trees. CT scan showed a small low density area which, limited to the basal part of the left temporal and occipital lobes, was complicated partially by a high density area that was thought to be calcified. On T2-weighted MRI images, the lesion was shown as a small oval-shaped high signal intensity area surrounded by a low signal intensity area, and from its characteristic findings, a cavernous angioma was suspected. On the EEG, epileptic discharge was observed in the area limited to the left occipital region when elementary visual hallucinations occurred, and high amplitude diffuse slow waves were revealed predominantly on the left when complex visual hallucinations developed. It was thought that elementary visual hallucinations occurred in this patient following epileptic discharge of the occipital lobe, and complex visual hallucinations developed secondarily to the discharge which expanded from the occipital lobe to the surrounding area. Considering the investigation of non-epileptic visual hallucinations that are observed in the hemianopic visual field, we believe that disturbances of function of the temporo-parietal lobes around the occipital visual cortex has an important role in causing the development of complex visual hallucinations.

Brain Neoplasms↗

[Mediastinitis treated by an omental transfer following CABG using the right gastroepiploic arterial graft].

We treated four cases with mediastinitis after coronary artery bypass grafting using the right gastroepiploic artery. These four patients were treated with the pedicled omentum. Omental transfer was successful in three cases. After the harvest of the right gastroepiploic arterial graft, the residual omentum was viable. The residual omentum was applicable for the treatment of mediastinitis.

Aged↗

[Indices allowing early detection of chronic pulmonary emphysema].

To establish criteria allowing early detection of pathologically significant alterations in pulmonary emphysema caused by smoking, pulmonary-function tests and high-resolution computed tomography were done in 104 subjects categorized into three groups: nonsmoking healthy adults, smokers with a normal FEV1%, and smokers with a low FEV1% (cross-sectional analysis). Fifty-six of the 104 patients underwent pulmonary-function testing and high-resdution computed fomography once per year for 3 years (longitudinal analysis). Cross-sectional and longitudinal analyses showed that abnormalities in functional residual capacity, in single-breath diffusing capacity for carbon monoxide, and in the average tomographic density of sections in the lower lung fields obtained after a deep inspiration could be used to predict whether the disease would reach an advanced stage, even if the patients had no significant symptoms at the time of testing. Relative areas of low-attenuation regions, which were alleged to directly reflect the size of emphysematous areas, appear not to be useful for early detection of pathological emphysema.

Chronic Disease↗

Analysis of cis-acting regions upstream of the rat Na+/K(+)-ATPase alpha 1 subunit gene by in vivo footprinting.

By means of in vivo footprinting, we examined the putative cis-acting DNA elements located between -50 and -122 of rat Na+/K(+)-ATPase alpha 1 subunit gene ATP1A1. Proximal and distal GC box sequences and a consensus sequence for the active transcription factor (ATF) were protected for all the tissues examined (kidney, brain and liver). Putative cooperation between two binding factors on the ATF site and the proximal GC box was observed. The overall in vivo footprinting profiles of the three tissues did not exhibit any marked differences that could account for the variation in the extent of tissue-specific transcription. The alpha 1 regulatory element (ARE) found by Suzuki-Yagawa et al. does not appear to be an element responsible for tissue-specific regulation of the gene.

Animals↗

Unique binding of a novel synthetic inhibitor, N-[3-[4-[4-(amidinophenoxy)carbonyl]phenyl]-2-methyl-2-propenoyl]- N-allylglycine methanesulfonate, to bovine trypsin, revealed by the crystal structure of the complex.

Trypsin and N-[3-[4-[4-(amidinophenoxy)carbonyl]phenyl]-2-methyl-2-propenoyl]- N-allylglycine methanesulfonate (1), a newly designed and orally active synthetic trypsin inhibitor, were cocrystallized. The space group of the crystal is P2(1)2(1)2(1) with cell constants a = 63.74 A, b = 63.08 A, and c = 69.38 A, which is nearly identical to that of the orthorhombic crystal of guanidinobenzoyltrypsin. The structure was refined to a crystallographic residual R = 0.176. The refined model of the 1-trypsin complex provides the structural basis for the reaction mechanism of 1. On the basis of the present X-ray results, it is proposed that the potent inhibitory activity of 1 is mainly due to the formation of an acylated trypsin through an "inverse substrate mechanism" and its low rate of deacylation.

Allylglycine↗

Generation and characterization of a host cell-dependent gag gene mutant of human immunodeficiency virus type 1.

An in-frame gag gene mutant of human immunodeficiency virus type 1, which carries two amino acid substitutions in the center of the p24 coding region, was constructed in vitro, and its replication properties in several cell lines were examined. In CD4-negative SW480 cells transfected with the mutant clone, synthesis and processing of viral gag, pol, and env proteins occurred normally, and viral particles were produced. Virions derived from the transfection displayed a severe replication defect when inoculated into some CD4-positive cell lines (H9 and Molt4 clone 8), but in other lines (A3.01 and M8166), the mutant virus grew fairly well. The mutant was demonstrated to be defective at an early infection phase (from adsorption to integration) in Molt4 clone 8 cells but was normal in A3.01 cells. These results indicated that the Gag-p24 protein of human immunodeficiency virus type 1 plays an important role at the early infection phase in a cell-dependent manner.

Amino Acid Sequence↗

Homozygous deletions of p16/MTS1 gene are frequent but mutations are infrequent in childhood T-cell acute lymphoblastic leukemia.

Fifty-six primary childhood T-cell acute lymphoblastic leukemia (T-ALL) samples and 17 T-ALL cell lines were examined for mutations and homozygous deletions of the p16/MTS1 gene using polymerase chain reaction single-strand conformation polymorphism and Southern blot analysis. Homozygous deletions were found in 22 primary samples (39%) and in 10 cell lines (59%). In contrast, mutations including small deletions and/or insertions were identified in only 4 primary samples (7%) and in 2 cell lines (12%). Mutations included samples (7%) and in 2 cell lines (12%). Mutations included one nonsense mutation at codon 72, one missense mutation at codon 58, one deletion (29 bp from codon 52-61), one insertion (7 bp into codon 50), and two deletion/insertions (codon 63 and intron 1). Four of the six mutations caused subsequent stop codon and presumably produced truncated p16 protein. Our results suggest that p16 gene alterations are involved in the development of T-ALLs and that the inactivation of the p16 gene occurs mainly through homozygous deletions rather than mutations.

Base Sequence↗